[Entrez medline Query] ==ATRIAL FIBRILLATION== Am J Cardiol 1998 Aug 20;82(4A):7I-8I Measures of drug efficacy in treating atrial fibrillation. Waldo AL Department of Medicine, Case Western Reserve University/University Hospitals of Cleveland, Ohio 44106-5038, USA. Atrial fibrillation (AF) tends to recur in at least one half of the patients being treated with an antiarrhythmic agent. However, if the patient being treated is appropriately anticoagulated, and if during recurrence the ventricular response rate is controlled, a recurrence rarely requires emergent treatment. Rather, the AF recurrence can most often simply be considered a clinically important nuisance. Therefore, recurrence of AF during antiarrhythmic drug therapy should not be considered drug failure per se. Instead, the frequency and severity of recurrence constitute the measure of efficacy. Occasional recurrence may be clinically acceptable and preferable to persistent AF or frequent episodes of paroxysmal AF. Because occasional recurrence of AF should not be considered failure of drug therapy, simple outpatient cardioversion of the AF with restoration of sinus rhythm is recommended should recurrence occur and the AF persist. Simple therapies, such as acute cardioversion to restore sinus rhythm, should be considered a part of the expected long-term therapy of the patient with AF. Finally, the drug of choice should be one that is well tolerated, easy to take (preferably only once or twice a day), and has the fewest potential side effects, particularly serious adverse effects. ------------------------------------------------------------------------ Neurology 1998 Sep;51(3):674-681 Prevention of stroke in patients with nonvalvular atrial fibrillation. Hart RG, Sherman DG, Easton JD, Cairns JA University of Texas Health Science Center, San Antonio 78284-7883, USA. [Medline record in process] OBJECTIVE: To review the risk and pathogenesis of stroke associated with nonvalvular atrial fibrillation (AF) and the efficacies and risks of stroke prevention strategies. BACKGROUND: About 16% of ischemic strokes are associated with AF; AF is an independent risk factor for stroke. METHODS: Review of the literature, focusing on 13 randomized trials of antithrombotic therapy. RESULTS: The overall risk of stroke in AF patients averages about 5%/y, but with wide variation depending on the presence of coexistent thromboembolic risk factors. AF patients with low (about 1% per year), moderate (about 3% per year), and high (about 6% per year) stroke risks have been identified, but the generalizability of risk stratification schemes to clinical practice has not been fully assessed. AF patients with prior stroke or transient ischemic attack, even if remote, are at highest risk (about 12% per year). Adjusted-dose warfarin (target International Normalized Ratio [INR] 2-3) is highly efficacious for preventing stroke in AF patients (about 70% risk reduction) and is safe for selected patients, if carefully monitored. Aspirin has a modest effect on reducing stroke (about 20% risk reduction). The numbers of AF patients that would need to be treated with warfarin instead of aspirin for 1 year to prevent one ischemic stroke are about 200, 70, and 20 for those with low, moderate and high risk, respectively. CONCLUSIONS: Many patients with nonvalvular AF have substantial rates of ischemic stroke. Stratification of stroke risk identifies AF patients who benefit most and least from lifelong anticoagulation. Warfarin is recommended for high-risk AF patients who can safely receive it. Aspirin may be indicated for those with a low stroke risk and for those who cannot receive warfarin. For AF patients considered to have a moderate risk of stroke, individual bleeding risk during anticoagulation and patient preference should particularly influence the choice of antithrombotic prophylaxis. ------------------------------------------------------------------------ Curr Opin Lipidol 1998 Aug;9(4):325-328 Are risk factors for stroke and coronary disease the same? Qizilbash N SmithKline Beecham Pharmaceuticals, Oxford, UK. nawab_qizilbash-1@sbphrd [Medline record in process] Many risk factors operate in both coronary heart disease and stroke, especially ischaemic stroke--age, sex, social class, blood pressure, pre-existing vascular disease (angina, myocardial infarction, cardiac failure, diabetes and peripheral vascular disease, transient ischaemic attack and stroke), atrial fibrillation and fibrinogen, smoking, alcohol and height. Total cholesterol has also recently been recruited to this list. The various mechanisms involved in stroke and its subtypes and the epidemiological problems in evaluating aetiological factors in stroke make the comparison with coronary heart disease more difficult. The recent discrepancy between much of the epidemiology and the clinical trials evaluating the role of lipids in stroke has spurred the systematic review (meta-analysis) of major prospective observational studies. These will provide a clearer assessment about the quantitative comparison of some of the more important risk factors for stroke and coronary heart disease in the near future. ------------------------------------------------------------------------ Am J Cardiol 1998 Aug 20;82(4A):3I-6I Perspectives and controversies in atrial fibrillation. Prystowsky EN Clinical Electrophysiology Laboratory, Northside Cardiology, St. Vincent Hospital, Indianapolis, Indiana 46260, USA. Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. The 3 basic tenets of therapy are (1) restoration and maintenance of sinus rhythm; (2) ventricular rate control; and (3) prevention of thromboembolism. Maintenance of sinus rhythm appears preferable to rate control alone in patients with significant symptoms caused by AF. Complete suppression of AF with drug therapy for >6 months is unusual, but it is not the sole criterion of success. As with other chronic cardiac disorders such as angina and heart failure, a marked reduction in frequency and duration of episodes of AF will likely translate into an excellent clinical outcome. The major risk of antiarrhythmic drug therapy is ventricular proarrhythmia, which is seen most frequently in patients with substantial left ventricular dysfunction. Torsade de pointes is the most frequent proarrhythmia that occurs with antiarrhythmic agents that prolong ventricular repolarization and the QT interval. To minimize the risk of proarrhythmia, antiarrhythmic drugs are started in-hospital in patients with significant heart disease, and agents are selected based on certain patient characteristics. For example, the drugs initially selected for patients with heart failure and coronary artery disease are amiodarone and sotalol, respectively. Two approaches may be used to decrease the thromboembolic risk associated with cardioversion of AF to sinus rhythm. In the conventional method, warfarin is given (INR 2.0-3.0) for 3 weeks before and at least 4 weeks after cardioversion. An alternative approach employs transesophageal echocardiography to rule out left atrial thrombi before cardioversion. Both methods appear reasonable and safe, and I prefer the conventional and transesophageal echocardiography-guided approaches for outpatients and in-hospital patients, respectively. ------------------------------------------------------------------------ Stroke 1998 Sep;29(9):1827-1832 Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke. Lightowlers S, McGuire A Department of Geriatric Medicine, Newham General Hospital, London, UK. BACKGROUND AND PURPOSE: A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. METHODS: We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. RESULTS: The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. CONCLUSIONS: For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group. ------------------------------------------------------------------------ J Cardiovasc Electrophysiol 1998 Aug;9(8 Suppl):S177-S186 Quality of life in patients with atrial fibrillation. Jung W, Luderitz B Department of Medicine-Cardiology, University of Bonn, Germany. [Medline record in process] INTRODUCTION: The efficacy of a treatment is based primarily on objective criteria such as mortality and morbidity. Besides these criteria, the interest in measuring quality of life in relation to health care has increased in recent years. METHODS AND RESULTS: Although the concept of quality of life inherently is subjective and definitions vary, it generally is agreed that quality of life is a multidimensional construct. The impact of atrial fibrillation (AF) on quality of life has not been evaluated widely using validated methods. Therefore, an international prospective study was designed to assess quality of life over time in patients with AF using validated generic measures and specific conducted disease scales. In addition to a standard demographic questionnaire, patients will complete two predictive scales at baseline and four outcome scales at baseline, and 3-, 6-, and 12-month follow-up. An AF severity score based on subjective and physician-recorded assessments will be used to classify the patient's burden of AF as mild, moderate, or severe. CONCLUSION: Rigorous yet practical approaches are needed to allow for a comprehensive understanding of quality of life in patients with AF. The international study design outlined in this review article represents an attempt to systematically address quality of life in patients with AF and may serve as an example of the types of measures that may be useful in assessing quality of life in patients with AF. ------------------------------------------------------------------------ J Cardiovasc Electrophysiol 1998 Aug;9(8 Suppl):S86-S96 Role of anticoagulant therapy in atrial fibrillation. Kottkamp H, Hindricks G, Breithardt G Department of Cardiology and Angiology, Hospital of the Westfalische Wilhelms-University, and the Institute for Arteriosclerosis Research, Munster, Germany. [Medline record in process] Atrial fibrillation belongs to the group of cardiovascular diseases that most frequently predispose to arterial thromboembolic events. Within the last years, the AFASAK, BAATAF, SPAF I, SPINAF, and CAFA trials have consistently demonstrated a significant, approximately 70%, risk reduction for stroke on oral anticoagulation in patients with nonrheumatic atrial fibrillation. This benefit by far outweighed the slight increase in annual major hemorrhage. Recently, additional trials (SPAF II, EAFT, SPAF III, and others) have shed further light on important questions concerning risk factors, secondary prophylaxis, the optimal intensity of anticoagulation, and the role of aspirin and other antiplatelet drugs. The main results of these studies are discussed in this review. The majority of patients with atrial fibrillation are > 65 years of age and have other clinical or echocardiographic risk factors. In these patients, adjusted-dose warfarin with target international normalized ratios (INRs) 2.0 to 3.0 is effective and safe. The risk of stroke rises with INR values < 2.0, whereas INR values > 3.0 result in an increase in intracerebral hemorrhages, especially in the very elderly. In contrast, no anticoagulation seems warranted in younger atrial fibrillation patients < 60 years of age without any clinical or echocardiographic risk factor. An overview of all randomized trials that compared aspirin with placebo and/or adjusted-dose warfarin indicates that adjusted-dose warfarin is approximately 50% more effective than aspirin for primary and secondary prevention of stroke, at least in patients with atrial fibrillation who have clinical risk factors. Therefore, oral anticoagulation clearly is the therapy of choice for prevention of thromboembolism in patients with atrial fibrillation. ------------------------------------------------------------------------ Circulation 1998 Aug 4;98(5):479-486 Role of echocardiography in patients undergoing elective cardioversion of atrial fibrillation. Silverman DI, Manning WJ Cardiology Division, John Dempsey Hospital and University of Connecticut Health Center, Farmington, USA. Echocardiography has emerged as a fundamental tool in the evaluation of patients with atrial fibrillation (AF). Transthoracic echocardiography remains a primary tool for the evaluation and management of many patients presenting with their first episode of AF, but it is not adequate for exclusion of atrial thrombi. TEE offers excellent visualization of the atria and accurate identification or exclusion of thrombi. In concert with therapeutic anticoagulation, a TEE-guided approach to early cardioversion appears to have a safety profile similar to that of conventional therapy (1 month of precardioversion warfarin). The TEE-guided approach offers the advantages of simplified anticoagulation management and shorter duration of sustained AF, thereby allowing for a more rapid recovery of atrial mechanical function. Warfarin should be continued for 1 month after cardioversion to allow for more complete recovery of atrial function and for prophylaxis should the patient revert to AF. Cost-effectiveness models demonstrate that TEE-guided cardioversion represents a cost-effective strategy, but only if the transthoracic echocardiogram is omitted. For patients with a thrombus on the initial TEE, follow-up TEE (to document thrombus resolution) is recommended before cardioversion. ------------------------------------------------------------------------ Am Fam Physician 1998 Aug;58(2):471-480 Drugs for conversion of atrial fibrillation. Dell'Orfano JT, Luck JC, Wolbrette DL, Patel H, Naccarelli GV Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. Atrial fibrillation is the most common arrhythmia in patients visiting a primary care practice. Although many patients with atrial fibrillation experience relief of symptoms with control of the heart rate, some patients require restoration of sinus rhythm. External direct current (DC) cardioversion is the most effective means of converting atrial fibrillation to sinus rhythm. Pharmacologic cardioversion, although less effective, offers an alternative to DC cardioversion. Several advances have been made in antiarrhythmic medications, including the development of ibutilide, a class III antiarrhythmic drug indicated for acute cardioversion of atrial fibrillation. Other methods of pharmacologic and nonpharmacologic cardioversion remain under development. Until the results of several large-scale randomized clinical trials are available, the decision to choose cardioversion or maintenance of sinus rhythm must be individualized, based on relief of symptoms and reduction of the morbidity and mortality associated with atrial fibrillation. ------------------------------------------------------------------------ Semin Interv Cardiol 1997 Dec;2(4):185-193 Spatio-temporal patterns of atrial fibrillation: role of the subendocardial structure. Skanes AC, Gray RA, Zuur CL, Jalife J Department of Pharmacology, SUNY Health Science Center at Syracuse 13210, USA. [Medline record in process] Despite many years of research and speculation, the precise mechanisms underlying atrial fibrillation remain elusive. Prevalent understanding relies on assumptions, which are based on two-dimensional numerical simulations and on the idea that atrial fibrillation is the result of total disorganization of electrical activity, with multiple wavelets wandering randomly throughout the atria. However, recent studies both clinical and basic, have suggested that focal mechanisms, either re-entrant or automatic, may explain fibrillatory activity in some cases. Here we review the major hypotheses that have prevailed at one time or another to explain this complex arrhythmia and discuss some recent experimental results that strongly suggest that, whatever the electrophysiological basis of atrial fibrillation may be, it must involve complex patterns of propagation through the intricate multidimensional anatomical structure of the atria. ------------------------------------------------------------------------ Geriatrics 1998 Jul;53(7):53-60 Atrial fibrillation: preventing thromboembolism and choosing nondrug therapies. Chandramouli BV, Kotler MN Department of medicine, Albert Einstein Medical Center, Philadelphia, USA. A major consequence of atrial fibrillation (AF) is stroke. For stroke prevention in AF, the American Heart Association recommends aspirin, 325 mg/d, for low-risk patients. For all others, anticoagulation with warfarin to a target INR of 2 to 3 is recommended if warfarin is not contraindicated. Approximately 0.3% of patients receiving warfarin suffer intracranial hemorrhage. For restoration of sinus rhythm in recent AF, direct current cardioversion is the treatment of choice if a trial of antiarrhythmic drug therapy has failed or is contraindicated. Potential complications include thromboembolism, ventricular arrhythmia, and pulmonary edema. Permanent pacemakers can be used to control conduction disturbances such as sick sinus syndrome and to prevent paroxysmal AF. Radiofrequency AV nodal ablation provides symptomatic relief for some patients with chronic or paroxysmal AF. Surgical techniques are also being developed for AF. These include left atrial isolation and the corridor and maze procedures. ------------------------------------------------------------------------ Am Fam Physician 1998 Jul;58(1):130-136 Indications for anticoagulation in atrial fibrillation. Akhtar W, Reeves WC, Movahed A East Carolina University School of Medicine, Greenville, North Carolina, USA. Factors associated with an increased risk of thromboembolic events in patients with atrial fibrillation (AF) include increasing age, rheumatic heart disease, poor left ventricular function, previous myocardial infarction, hypertension and a past history of a thromboembolic event. Patients with AF should be considered for anticoagulation or antiplatelet therapy based on the patient's age, the presence of other risk factors for stroke and the risk of complications from anticoagulation. In general, patients with risk factors for stroke should receive warfarin anticoagulation, regardless of their age. In patients who are under age 65 and have no other risk factors for stroke, either aspirin therapy or no therapy at all is recommended. Aspirin or warfarin is recommended for use in patients between 65 and 75 years of age with no other risk factors, and warfarin is recommended for use in patients without risk factors who are older than 75 years of age. ------------------------------------------------------------------------ Cardiovasc Res 1998 Mar;37(3):567-577 Experimental evidence for proarrhythmic mechanisms of antiarrhythmic drugs. Nattel S Department of Medicine, Montreal Heart Institute, Quebec, Canada. The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved antiarrhythmic drug therapy to be developed, it is essential to understand the fundamental mechanisms that cause proarrhythmic reactions to antiarrhythmic drugs. The present article reviews the experimental evidence that has been obtained regarding the mechanisms of proarrhythmia. The evidence available provides important insights, and points to potential strategies for developing newer and safer antiarrhythmic compounds.